Metformin treatment of patients with hand osteoarthritis: A randomised, placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Bispebjerg Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

3 May 2024 → ongoing

Decision date (initial)

2024-04-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To compare the effect of metformin, relative to placebo, on finger joint pain of the target hand measured as change in a visual analogue scale (VAS) after 16 weeks of treatment, in patients with painful hand OA.

Conditions and MedDRA coding

Osteoarthritis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. Study participants will have a diagnosis of hand OA. Diagnosis will be confirmed by a medical doctor at baseline and participants must fulfil the American College of Rheumatology (ACR) criteria for hand OA (35): • Hand pain, aching or stiffness on most days the previous 4 weeks And at least 3 of the following features: • Hard tissue enlargement of ≥2 of the 10 selected joints* • Hard tissue enlargement of ≥2 of the 10 DIP joints • Fewer than 3 swollen metacarpophalangeal (MCP) joints • Deformity of at least 1 of 10 selected joints* *The 10 selected joints are the second and third DIP, the second and third PIP, and the first carpometacarpal joints of both hands. An individual will be eligible for study participation if he/she meets the following criteria: 1. Age ≥18 years 2. Hand OA according to the ACR criteria above 3. Average finger (2 to 5) pain ≥4 on a 0-10 numeric rating scale (NRS where 10 is worst pain) over the past 30 days 4. Metformin naive

Exclusion criteria 1

1. A participant will be excluded from the study if he/she meets any of the following criteria listed below. Known diseases will be based on diagnosis registered in the participants health journal. If an exclusion diagnosis is suspected, necessary diagnostics will be performed before inclusion in the study. Comorbidities 1. History of, or current signs of medical disease that may affect joints, e.g. rheumatoid arthritis, gout, psoriatic arthritis 2. Psoriasis 3. Known malignancy (except successfully treated squamous or basal cell skin carcinoma) 4. Drug or alcohol abuse in the last year 5. Existing nerve entrapment syndromes (e.g. carpal tunnel syndrome) 6. Known diabetes 7. Generalised pain syndromes such as fibromyalgia 8. Known peripheral neuropathies 9. Known allergies towards the interventions 10. Gastric bypass or other malabsorption syndrome 11. In case of pharmacological weight loss medication (e.g. glucagon like peptide-1 (GLP-1) analogues) or pharmacological osteoporosis medication, dosage must have been stable for 3 months without any plan of up-titration during the study period 12. Any other condition or impairment that, in the opinion of the investigator, makes a potential participant unsuitable for participation or obstructs participation e.g. psychiatric disorders. Surgical history 13. History of hand surgery in the target hand within 12 months prior to enrolment 14. History of arthroplasty, arthrodesis or surgical treatment of thumb base osteoarthritis in the target hand Management strategies 15. Use of systemic corticosteroids equivalent of ≥ 7.5 mg prednisolone daily within 3 months 16. Treatment with denosumab (Prolia/Xgeva) 17. Participation in experimental device or experimental drug study 3 months prior to enrolment 18. Intra-articular treatments of any kind of any joint of the target hand 3 months before inclusion 19. Current use of synthetic or non-synthetic opioids 20. Planning to start other treatment for hand OA in the study participation period 21. Planned CT scan with iodine contrast 22. Scheduled surgery on upper extremity of the target hand during study participation 23. Scheduled surgery requiring pause of metformin, e.g. surgery in general anaesthesia, during study participation Reproductive system 24. Pregnancy 25. Planned pregnancy within the study period, 3 months after end of study treatment for female fertile participant and 6 months after end of study treatment for male participant 26. Insufficient anti-conception therapy for female fertile participants within the study period and 3 months after end of study treatment  Sufficient anti-conception therapy consists of intra-uterine device (coil), hormonal anti-conception (birth control pills, implant, intra-uterine system, dermal patch, vaginal ring, or injections) or sexual abstinence  Female participants are considered infertile if they are postmenopausal or if they have undergone surgical sterilisation (bilateral salpingectomy, hysterectomy or bilateral oophorectomy)  Postmenopausal state is defined as no menses for 12 months without alternative medical cause before inclusion in the study 27. Insufficient anti-conception therapy for male participants within the study period and 6 months after end of study treatment  Sufficient anti-conception therapy consists of condom or sexual abstinence  Male participants are considered sterile if they have undergone surgical sterilisation (vasectomy) 28. Breast-feeding Blood analysis 29. Positive anti-cyclic citrullinated peptide (>10 kU/L) 30. eGFR <60 ml/min/1.73 m2 31. Vitamin B12 deficiency < 200 pmol/L 32. Hba1c ≥ 48 mmol/mol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in VAS finger joint pain of the target hand after 16 weeks of treatment (at the week 17 visit).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Bispebjerg Hospital

Sponsor organisation

Bispebjerg Hospital

Address

Borgmester Ib Juuls Vej 31

City

Herlev

Postcode

2730

Country

Denmark

Scientific contact point

Organisation

Bispebjerg Hospital

Contact name

The Parker Institute

Public contact point

Organisation

Bispebjerg Hospital

Contact name

The Parker Institute

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications